The main objective of this study is to detect major genes in the transmission of affective disorders. This goal will be attained by 1. ascertaining pedigrees segregating for the illness; 2. employing segregation analysis techniques aimed at unraveling the mode of inheritance; and 3. conducting linkage studies with DNA markers (restriction fragment length polymorphisms) in suitable pedigrees. Should linkage (or linkages) be established, the study will also aim to characterize the genetically linked cases on clinical/biological measures in an attempt to define homogeneous subsets of the disorder. Longer range goals will include the assessment of linked markers as risk predictors, the identification and characterization of the defective markers as risk predictors, the identification and characterization of the defective gene (or genes), searching for the gene's biological products, and assessing gene-environment interaction. The new DNA technology coupled with other recent methodologic advances, such as approaches to systematically obtaining family data, structured interviews and precise diagnostic criteria, and the availability of a range of genetic modes, holds much promise for unraveling the genetic mechanisms that underlie subtypes of affective illness. This, in turn, would have major implications for the etiology, nosology, pathophysiology, and, possibly, prevention and treatment of affective disorders.